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M Nitta

Publications and source records attributed to M Nitta.

At least 19 recordsLinked to original sources

Detection of bcr/abl fusion transcripts by semiquantitative multiplex RT-PCR combined with a colormetric assay in Ph positive leukemia.

We studied the feasibility of the clinical application of a new bcr/abl analysis system, C-TRAK t(9;22), consisting of a multiplex RT-PCR and a colormetric assay. With this system, bcr/abl transcripts could be detected in all of 24 cytogenetic Philadelphia chromosome (Ph) positive leukemia patients and in none of eight Ph negative patients. Multiple bcr/abl transcripts could be detected in three of the 24 Ph positive patients, the fusion of bcr exon 1 to abl exon 2 (e1a2 junction) dominated that of bcr exon 13 to abl exon 2 (b2a2 junction) in two cases and that of bcr exon 14 to abl exon 2 (b3a2 junction) and b2a2 dominated e1a2 in one case. This system was sensitive enough to be able to detect even one bcr/abl transcript-producing cell in 50000 bcr/abl negative background cells, thus making it suitable for semiquantitative evaluation. Minimal residual disease (MRD) was monitored in one Ph positive leukemia patient who underwent allogenic bone marrow transplantation (allo-BMT). After allo-BMT, a weak positivity of the bcr/abl transcript continued with no clinical relapse; this result was consistent with that of a conventional nested PCR assay using ethidium bromide staining. Including all the procedures for RNA extraction, it took only about 10 h to detect the bcr/abl transcripts. Our findings indicate that this bcr/abl analysis system provides a quick and sensitive method for screening bcr/abl transcripts and possibly for monitoring MRD in Ph positive leukemia patients.

Acute Disease

Microsatellite instability is rare in the clinical course of myelodysplastic syndrome studied with DNA from fresh and paraffin-embedded tissues.

Microsatellite instability (MSI) has been reported to occur in various types of malignant neoplasms. We performed a polymerase-chain-reaction-based assay for MSI between the initial and the most recently available ("latest") samples from 23 patients with myelodysplastic syndrome (MDS). Of these patients, 15 were informative at more than three microsatellite loci. Seven patients showed an increase in leukemic cells while 8 patients did not during the interval between the two analyses. Only 1 of the patients, who had refractory anemia with excess blasts, which changed to acute myelogenous leukemia, showed microsatellite alteration at the analysis times. Among all 23 patients, two alterations were detected in the 42 informative paired samples that showed an increase in leukemic cells (4.8%), while none was detected in the 59 paired samples without such an increase. In total, therefore only two alterations were detected among 101 informative paired samples (2%). This indicates that MSI is rare in the clinical course of MDS irrespective of disease status, and is consequently not a critical genetic event for disease progression in most MDS patients.

Adult

Transient appearance of CD3+CD8+ T lymphocytes with monoclonal gene rearrangement of T-cell receptor beta locus.

A benign, transient proliferation of atypical lymphocytes and a monoclonal rearrangement of the T-cell receptor beta (TRB) locus was found in a 60-year-old woman who presented with low-grade fever, anorexia and fatigue. A marked and transient atypical lymphocytosis (white blood cell count 90.5 x 10(9)/l) with CD8 surface antigen improved without specific treatment. Although tests for IgM antibodies to hepatitis A, varicella zoster, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all negative, a monoclonal gene rearrangement of TRB locus was observed in the DNA of the proliferated atypical lymphocytes by Southern blotting. The clonal rearrangement and the atypical lymphocytes disappeared after 14 d, and the patient has remained well for 7 years. These results suggest that monoclonal proliferation of CD8 lymphocytes can occur based on a non-neoplastic aetiology.

Blotting, Southern

Transcription factor CP2 is essential for lens-specific expression of the chicken alphaA-crystallin gene.

BACKGROUND: Lens-specific transcriptional activation of the chicken alphaA-crystallin gene is controlled by the distal and proximal enhancers, alphaCE1 and alphaCE2, respectively. Analysis using specific monoclonal antibodies against purified alphaCE1-binding factor alphaCEF1 revealed that alphaCEF1 is composed of two distinct subunits. RESULTS: We have demonstrated that one of the subunits of alphaCEF1 is encoded by chicken ubiquitous transcription factor CP2 (cCP2), which is homologous to mouse CP2, and human CP2/LBP-1/LSF-1. Electrophoretic mobility shift assays and cross-linking experiments showed that alphaCEF1 and bacterially expressed cCP2 form a tetramer. Overexpression of cCP2 activates transcription through alphaCE1, but a mutant cCP2 lacking the DNA-binding domain reduced the transcription to basal levels. Although cCP2 binds to the CP2 template from the mouse alpha-globin promoter, it fails to promote transcription through this template. Element substitution experiments between alphaCE1 and the CP2 template revealed that the lens-specific enhancer activity of alphaCE1 is due to the 6 bp sequence (-139/-134; lens-specific element (LSE)) adjacent to the 3' of the cCP2 binding site within alphaCE1. CONCLUSION: We have shown that the tetrameric transcription factor cCP2 is essential for lens-specific transcription of the chicken alphaA-crystallin gene, although it is ubiquitously expressed. We propose a model where cCP2 cooperates with a putative lens-specific factor which binds to LSE.

Amino Acid Sequence

[Hearing recovery in sudden deafness with profound hearing loss].

We investigated the hearing recovery in 51 patients with sudden deafness with the initial averaged five-frequency hearing levels worse than or equal to 100 dB. Twenty-two patients were treated in an outpatient setting with a peri-oral steroid, vasodilator, metabolic activator, and vitamin B. The remaining 29 patients were treated in the hospital with additional hyperbaric oxygenation therapy and/or Satellite ganglion block. The results were as follows. 1) The ultimate averaged five-frequency hearing levels were mainly distributed from 55 to 80 dB. Only seven patients showed ultimate hearing levels worse than 100 dB. Two patients achieved complete recovery better than 20 dB. 2) There was no significant difference in the hearing recovery between the patients treated in an outpatient setting and in the hospital. 3) The time interval until the hearing recovery began was distributed broadly between 2 and 28 days from the onset. While most of the patients who began to recover within 14 days from the onset showed ultimate hearing levels better than 80 dB, the patients who recovered after 14 days had worse hearing levels.

Adolescent

[Sweet's syndrome].

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Anti-Inflammatory Agents

Heat shock induces transient p53-dependent cell cycle arrest at G1/S.

Heat shock (43 degrees C, 45 min) induced transient nuclear accumulation of p53 in primary human fibroblasts without any clonogenically toxic effects. The accumulation of p53 reached a maximal level 3 approximately 5 h after heat shock, and returned to the basal level within 12 h. Following the increase in p53 level, cell cycle arrest at G1/S was observed in normal fibroblasts, whereas neither nuclear accumulation of p53 nor cell cycle arrest were observed in HeLa cells. By comparing cell cycle patterns of heat-treated mouse cells with different genotypes at the p53 locus (+/+, +/-, -/-), the observed cell cycle arrest at G1/S was demonstrated to be p53-dependent. Cell cycle arrest in normal human fibroblasts continued for nearly 24 h, resulting in a one day delay of cell growth compared with non-treated cells. Following enhancement of the p53 level, the amount of p21/WAF1/ CIP1 increased, and the high level of p21 was sustained for almost one day in a cell cycle-independent manner, suggesting the involvement of p21 in the inhibition of cell cycle progression by heat shock.

Animals

A randomized study comparing VMCP and MMPP in the treatment of multiple myeloma.

PURPOSE: To compare VMCP, a multidrug combination chemotherapy comprising vincristine (VCR), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL), with MMPP comprising MPH, ranimustine (MCNU), procarbazine, and PSL as induction, to elucidate the value of alternating combination chemotherapy, and to search for an appropriate maintenance therapy in multiple myeloma. METHODS: At 16 institutions in the Nagoya City area, we carried out a randomized trial of VMCP versus MMPP as the initial treatment. Patients who were refractory or resistant to the initial therapy were crossed over into the other arm (crossover trial). For patients who achieved a partial response (PR) or a minor response (MR) and in whom the paraprotein level ceased to decrease, the maintenance therapy was randomized either to an MPH/PSL combination (MP) or to alternating combination therapy (AT) with VMCP and MMPP. RESULTS: In the 94 evaluable patients of the 111 enrolled, the response rate (PR rate) was 27.7% (13/47) in the VMCP arm and 44.7% (21/47) in the MMPP arm (P = 0.0859). The crossover trial resulted in a PR rate of 15.8% (3/19) for the VMCP-->MMPP crossover and 14.3% (2/14) for the MMPP-->VMCP crossover. The median survival time was 23.4 months for those initially begun in the VMCP arm and 24.9 months for those in the MMPP arm, showing a tendency for better survival during a follow-up of 2-6 years with MMPP treatment, but without statistical significance. The survival time of patients with progressive disease was significantly shorter than that of patients with PR, MR or no change (NC). However, there was no significant difference in the survival rate among those who achieved PR, MR, or NC. As to the maintenance therapy, there was no significant difference in survival between MP therapy and AT. Patients who reached a plateau phase survived significantly longer than those who did not. Except for six cases of grade 3 or 4 neurotoxicity in the VMCP arm, there was no significant difference in the hematologic or gastrointestinal toxicity between the two arms. CONCLUSIONS: We conclude that VMCP is less effective for myeloma than MMPP as the induction treatment, that alternating noncrossresistant chemotherapeutic combinations do not offer an advantage in multiple myeloma, and that patients who reach a plateau phase have a significantly longer survival time.

Adult

A left atrial myxoma complicated with acute myocardial infarction.

A 43-year-old female, admitted because of acute infero-posterior myocardial infarction, showed angiographic findings of 100% occlusion of left circumflex artery. Echocardiographic findings showed inferior hypokinesis, while a large left intraatrial tumor was also observed. The coronary angiography on the 17th hospital day showed complete reperfusion of the culprit lesion without stenosis. On the 21st hospital day, the removal operation of the tumor was performed. Pathological findings showed typical cardiac myxoma, and the etiology of the occlusion at the culprit vessel was presumed to be closely related to the existence of the left atrial tumor.

Adult

Idiopathic CD4+ T-lymphocytopenia in a non-Hodgkin's lymphoma patient.

We report a case of idiopathic CD4+ T-lymphocytopenia with malignant lymphoma (diffuse large, B-cell type) for which there was no evidence of human immunodeficiency virus type 1 or type 2 infection and no other known causes of immunodeficiency. She had never suffered from any opportunistic infection until the diagnosis of malignant lymphoma was made, and the CD4+ T-lymphocytopenia persisted after complete remission of the lymphoma. As the clinical features and immune status of the patient differed from those associated with the acquired immunodeficiency syndrome (AIDS)-related syndrome, we conclude that immunodeficiency in this case did not contribute to the opportunistic infection but may have been associated with the genesis of malignant lymphoma.

CD4-Positive T-Lymphocytes

[Clinical and histopathological studies of granular cell tumor of the tongue].

We studied the clinical and histopathological characteristics of granular cell tumor (GCT) of the tongue in 5 cases (2 males and 3 females) over a period of 25 years. The patients ranged in age from 8 to 44 years old. In 4 cases, the site of origin in the tongue was the anterior two thirds of the lateral border (UICC). In the remaining case, the tumor originated on the dorsal surface of the tongue (UICC). The tumor was 3-10 mm long and had an average diameter of 6mm. The lesions were painless. The cellular granules in all the tumors reacted positively to PAS regent and S-100 protein using immunohistological methods. Other immunohistological staining using anti-actin antibody showed cellular granules beneath the epithelium. In one case, these findings were especially marked in the portion that exhibited pseudo-epitheliomatous hyperplasia. There was a mixture of both positive and negative cells in the deep layer of the epithelium. Not all tumor cells stained with anti-desmin antibody, however, there appeared to be a direct transitions from stained striated muscle fibers to the tumor cells. Staining with anti-vimentin antibody was positive at the boundaries between cells and the positive granules in cells appeared in the dots. Two of the five, tumors were unencapsulated, and the other 3 were partially encapsulated. The constituent fibers of the capsule consisted of collagen fibers alone. Thus, the former 2 cases should be regarded as proliferative in nature, and the latter 3 as benign. These tumor cells were potentially very active beneath the epithelium. From the results of our immunohistological stainings, we concluded that myoepithelial cells might also be the source of GCT cells, although GCT cells have generally been reported to originate from muscle and nerve cells. We maintain that care must be taken when removing GCTs because there may be proliferative growth along the epithelium.

Adolescent

Cell proliferation detected by DNA polymerase alpha in acute leukemias.

Fifty-nine patients with acute leukemia were studied by flow cytometry using monoclonal antibody against DNA polymerase alpha. Since fresh and frozen cells showed identical flow cytometric histograms, 86 cryopreserved samples (39 from peripheral blood and 47 from bone marrow) were used in this study. The DNA polymerase alpha-positive population ranged from 16.3 to 84.7% in peripheral blood, and from 6.5 to 92.1% in bone marrow. A positive correlation (r = 0.80; p < 0.01) was found between DNA polymerase alpha-positive populations in peripheral blood and bone marrow from the same patient. This suggests that the DNA polymerase alpha-positive population in the bone marrow can be estimated from that in peripheral blood. A negative correlation was observed between the positive population in bone marrow samples and the time to reach a nadir (r = -0.58: p < 0.01), while a positive correlation was found between the tumor cell count in bone marrow and the DNA polymerase alpha-positive population (r = 0.64; p < 0.01) in patients who responded to chemotherapy.

Acute Disease

[Inflammatory sensory ataxic neuropathy presenting with alternating skew deviation on lateral gaze: a case report].

We report a 56-year-old female with chronic progressive sensory ataxic neuropathy presenting with alternating skew deviation on lateral gaze in the clinical course. She initially developed dysesthesias in the hands and feet asymmetrically, then gait disturbance developed over several months, and she was admitted to our hospital. Neurological examinations revealed profound deep sensory loss and mild superficial sensory disturbance with the absence of deep tendon reflexes, but muscular strength was completely preserved. EMG showed no evoked response of sensory nerve velocities and normal motor nerves. Sural nerve biopsy showed moderate demyelination with mild infiltration of inflammatory cells, and no vasculitis or onion bulb formation. CSF examination revealed elevation of cell counts and protein with marked intrathecal IgG synthesis and myelin basic protein, but finding of neurosyphillis. Serological examinations did not show any evidence of collagen disease, paraproteinemia, retrovirus infections or Lyme disease. Serum antiganglioside antibodies and anti-Hu antibody were negative. No evidence of malignancy was seen by radiological examinations and assays of tumor markers. In the weeks after admission, gait ataxia progressively worsened, and then she developed alternating skew deviation on lateral gaze, suggesting that the CNS was involved. No responsible lesion was detected on MRI. Corticosteroid administration improved not only the CSF findings, but also the neurologic symptoms, including the alternating skew deviation on lateral gaze. Although the disease entity was not identified, inflammatory demyelinating processes and immune-mediated mechanisms were considered to play important roles.

Anti-Inflammatory Agents

Truncated XPA protein detected in atypical group A xeroderma pigmentosum.

XPA protein from a patient with typical group A xeroderma pigmentosum (XP) and three atypical group-A XP patients were analysed. Immunoblot analysis of XPA proteins revealed that a typical group-A XP patient showed no XPA protein band, while a smaller, truncated XPA protein, which appears to be responsible for mid skin lesions and minimal neurological abnormalities, was detected in cells from three atypical group-A XP patients. Furthermore, the difference in the amount of truncated XPA protein correlated with the mildness of neurological manifestations in these three atypical group-A XP patients. The results suggest a correlation between clinical manifestations and qualitative and quantitative abnormalities of XPA protein products.

Adolescent